• the forces that shape microbial communities
• why that variation matters

• Why do we see the diversity that we do within our communities?
• Why are instances of these communities so different?
• What if we could take community X from environment A and put it in environment B?
• What if we could take community X and start over in environment A?
• Can we change the direction that community X takes to make it look more like community Y?

• Genetics/Evolution
• Diet (e.g. vegan vs. SuperSizeMe)
• Environmental exposures (e.g. rural vs. urban)
• Life history (e.g. breast vs. bottle fed, antibiotics)
• Immune system
• Very difficult to separate these forces to determine their relative importance

• Neutral theory (Hubbell): The differences between trophically similar organisms are not important and the observed biodiversity is the product of each species taking a random walk (e.g. Island biogeography)
• Community assembly rules (Diamond): Competition is the primary force that shapes the structure of communities and populations will seek to minimize niche overlap (e.g. Forest succession)

• Should sound analogous to anyone familiar with the rift between the neutral and selection-based models of molecular evolution. The truth is somewhere in the middle

Palmer et al. (2007) PLoS Biology

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Marino et al. (2014) PNAS

"16S rRNA surveys of gut samples obtained from mice in both diet groups revealed that engraftment of the human gut microbiota was largely successful: All bacterial phyla, 11 of 12 bacterial classes, and 88% (58 of 66) of genus-level taxa detected in the donor sample were detected among the recipient mice"

Turnbaugh et al. (2009) Sci. Transl. Med

• Humans are a pain
• Unable to differentiate between the microbiota of animals living in a similar environment and consuming a similar diet
• The similarity of community structure between co-housed germ free mice colonized with murine cecal contents increases over time
• The ability to colonize germ-free mice with diverse microbiota is an attractive method for studying community assembly

1. How well do germ-free mice resemble their human donors?
2. Does intra-individual variation stabilize with time?
3. Does inter-individual variation, within a cage, stabilize with time?
4. How reproducible is community assembly across cages when using the same donor?
5. How important is host genetics in shaping community struture?
6. Are the "climax" communities more similar to each other than the donors were to each other?

• Colonize germ-free mice with feces from 11 human donors
  • 3-5 mice per cage
  • 1-4 cages per donor
• Obtain stool samples for ~20 days
• Sequenced the V4 region of the 16S rRNA gene on a MiSeq using Kozich et al. (2013) protocol
  • Error rate of ~0.01%
  • Data analyzed in mothur

1. How well do germ-free mice resemble their human donors? Not so much
2. Does intra-individual variation stabilize with time? Yes
3. Does inter-individual variation, within a cage, stabilize with time? Yes
4. How reproducible is community assembly across cages when using the same donor? Very
5. How important is host genetics in shaping community struture? In this case, not so much
6. Are the "climax" communities more similar to each other than the donors were to each other? Uh, actually the opposite

• Have replicated C57Bl/6 vs. Swiss Webster experiment with an additional stool sample
• Would be interesting to know how different the immune profile is for these various "climax" communities
• Think... different.

• “…it would appear to be a pointless and doubtful exercise to examine and disentangle the apparently random appearing bacteria in normal feces and the intestinal tract, a situation that seems controlled by a thousand coincidences.”
• “Yet I have nevertheless devoted myself now for a year virtually exclusively to this special study, it was with the conviction that the accurate knowledge of these conditions is essential, for the understanding of not only the physiology of digestion…, but also the pathology and therapy of microbial intestinal diseases.”
• Theodore Escherich, 1885

Palmer et al. (2007) PLoS Biology

• This presentation was prepared in R using the knitr and slidify packages.
  • It is available through our github repository
  • Once the manuscript is submitted the document (and paper) will be fully executable
  • write.paper is a reality
• If a first year grad student downloaded your sequence data from your last paper, would they be able to reproduce your results? Here are some examples from our lab:
  • Wild Peromyscus paper
  • Human community type paper